World Oncology Forum 2015
Chemoprevention in breast cancer and possible vaccine for prostate cancer
Dr Leslie Ford - National Cancer Institute, Rockville, USA
Over my career I’ve been instrumental in implementing some of the largest primary prevention clinical trials for cancer of the breast as well as cancer of the prostate.
What is the focus of prevention now?
Given the high cost and large sample sizes or large number of people that we need to conduct primary prevention trials we’ve now shifted our focus somewhat to what we call precision prevention. So using molecular science to better identify individuals that are at risk of developing cancer and also to focus in on targets and drugs that might interact with those targets so that we can have more focussed clinical trials and quicker results. But that’s easier said than done.
What does this entail in breast cancer?
In breast we’ve been focussing more on the original clinical trial with tamoxifen was a targeted agent, it targets the oestrogen receptor so that sometimes is lost in the discussions because it was done so long ago. But now we’re trying to define the population that we intervene on better, so focussing more on women that have preneoplastic lesions like lobular carcinoma in situ or atypical hyperplasia or even ductal carcinoma in situ which is really a precancerous lesion and not yet a frank cancer. So that hopefully will reduce the number of people that we need in order to study new drugs.
We also have a new emphasis on what we call immunoprevention, so harnessing the tumour immune system and the tumour associated antigens to target earlier lesions and prevent the progression to cancer. There are some interesting early phase trials being done in breast and prostate cancer.
Where is the focus in the case of prostate cancer?
The prostate is a tumour associated antigen, the vaccine is called PROSTVAC. It has been developed in our Centre for Cancer Research at the NIH and completed a treatment trial. We’re waiting for the results so it’s still under FDA regulation but we’ve just started a trial using it in a population of men who have been diagnosed with low grade prostate cancer who have chosen what we call watchful waiting or expectant management. So, again, a high risk population and one that has cancer but not one that has chosen to be treated.
What do you think the future holds for prevention?
My particular interest, obviously, is in what we call chemoprevention, drug interventions, vaccine interventions. I focus very little on lifestyle and diet, which is another huge area, and the NIH does support that. I like to think of it more in terms of vaccines, drugs, identifying who is destined to get cancer, understanding these preneoplastic lesions. There are a number of cancers now where we can identify the non-invasive phenotype, whether it’s Barrett’s oesophagus for adenocarcinoma of the oesophagus, the LCIS and DCIS in breast cancer or these low grade prostate tumours. Also the new lesions that we’re uncovering as a result of lung cancer screening, and trying to intervene on those lesions in order to prevent the invasion to frank cancer.
What about the issue of finding lesions in blood which don’t actually lead to cancer?
That’s a big focus of our recent research agenda and, as some people call it, over-diagnosis. A lot of people resent that term because they have gotten a diagnosis, they are told they have cancer, what do you mean over-diagnosis? So I think the better term for it and what we are now talking about is the cellular and molecular characterisation of lesions that are identified because of screening. As x-rays get more sensitive or CT scans or biopsies, we are identifying lesions that are not normal. Some might be invasive but they’re not all destined to be lethal. There’s a great need to be able to tell somebody up-front this is one you have to worry about, this is one you don’t. It doesn’t seem like grade, one of our traditional measures, histological grade, is enough. So we’ve just launched a big research initiative on the cellular and molecular characterisation of screen detected lesions, just started last week. So hopefully in the next three to four years we’ll have better information on prostate, lung and breast cancer.
